Molecular pathological analysis of follicular T-helper cells and their neoplasias

• Applicant: Professor Dr. Martin-Leo Hansmann, since 4/2016
• Subject Area: Pathology
• Term: from 2011 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 200714561

Angioimmunoblastic T-cell lymphoma (AITL) is one of the most frequent mature T-cell lymphomas. In the recent years much effort has been made to elucidate the molecular mechanisms that drive the pathogenesis of AITL. Most likely, neoplastic cells in AITL are derived from follicular T helper cells (TFH). These cells are characterized by the expression of CD4, ICOS, CXCR5 and Bcl6. Expression of ICOS is pivotal for the formation of TFH. Currently, there is no ICOS overexpressing mouse model available. The aims of the presented study are to assess a potential oncogenic role of ICOS in the transformation of mature T cells and to characterize the microenvironment of AITL. In the first funding period we were able to identify ICOS as a potential factor contributing to lymphoma formation by acting as a co-oncogene, as ICOS+ T cells appeared to be more susceptible to transformation than ICOS- T cells. Moreover, the number of germinal center B cells was strongly enlarged in stem cell transplanted animals overexpressing ICOS. Unfortunately, AITL represents a very rare lymphoma entity and we did not have the opportunity to analyze many fresh primary AITL single cell suspensions during the first funding period. Therefore, we established a new protocol to process frozen-thawed single cell suspensions, to be able to expand the number of analyzed cases, by receiving additional patient material from other institutions.In a second funding period further experiments will be tackled to improve our understanding of the co-oncogenic role of ICOS in the generation of AITL. Furthermore, applying our newly established freeze-thaw suspension protocol, the characterization of tumor cells and their microenvironment in AITL will be of major importance.

• DFG Programme: Research Grants
• Ehemalige Antragstellerinnen / Ehemalige Antragsteller: Dr. Sebastian Newrzela, from 11/2015 until 3/2016; Frederike Schmid, Ph.D., until 11/2015